Abstract

Whole body barometric flow through plethysmography is used to study respiratory output in rodent genetic and disease models. Turn-key commercial and custom systems are both used to gather multiple data streams for respiratory and metabolic parameters. Comprehensive and accurate data analysis is crucial to modelling congenital, pathogenic, and degenerative diseases. However, such studies produce large amounts of data that are time-consuming and diffcult to analyze. The investigator may use cumbersome hand annotation subject to observer bias or a series of software products to manage raw data, calculated data, statistical analysis, and graphing. Commercial software, however, is prohibitively expensive or bundled with turn-key systems limiting options for bespoke respiratory measurement systems. A lack of tools for high-throughput analysis of respiratory datasets remains a major challenge. Here, we present Breathe Easy, a novel open-source pipeline for processing raw recordings and associated metadata into operative outcomes, publication-worthy graphs, and robust statistical analyses including QQ and residual plots for assumption queries and data transformations. This pipeline uses a facile graphical user interface (GUI) for uploading data files, setting waveform feature thresholds, and defining experimental variables. After loading the GUI a, python-based program, Signal Analysis Selection and Segmentation Integration (SASSI) takes the user-settings and selects all quantitatively defined, quality breaths from each period of interest in the signal files. After SASSI, the STatistics and Graph Generator (STAGG) takes those breaths and performs linear mixed effects modeling based on user selections for each dependent variable of interest. Furthermore, our software can integrate non-respiratory experimental outcomes including quantified behavioral or gene expression data to test for breathing related associations. To validate breath selection and generate optimized default values, results from Breathe Easy were compared to manual selection by experts, which represents the current standard in the field. We show high quality breath selection and a significant reduction in quality of breaths that were rejected by the software. We also demonstrate Breathe Easy’s utility and capacity by examining a 2-year longitudinal study of an Alzheimer’s Disease mouse model to assess contributions of forebrain pathology in disordered breathing (600+ files; 1TB data). We show that, at least with this model of AD, there does not seem to be an association between forebrain pathology and respiratory outcomes. Breathe Easy offers a facile and highly customizable platform for automated handling and analysis of animal respiratory and metabolic data that sets the stage for high-throughput studies and machine learning approaches on large data sets. NIH: 1F32HL160073-01A1, R01HL130249 44617-S4. BCM McNair Scholar Program, March of Dimes Basil O'Connor Research Award, Parker B. Francis Fellowship, CJ Foundation for SIDS. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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